Clinical and Investigative Medicine最新文献

I hope you’re taking care and found some time to relax this summer. A new semester may mean a big transition—some folks are starting their graduate studies, re-entering clerkship, starting residency or entering a fellowship. For some, there will be little or no change at all; but just a continuation of one of the many phases of the physician-scientist training pathway. Whatever stage you’re at, the Clinical Investigator Trainee Association of Canada (CITAC) community is here to support and advocate for you!

Purpose: The use of intravenous immunoglobulins (IVIG) has increased significantly in the last decade causing challenges for blood suppliers to respond to the demand. Indications for which IVIG infusion should be given to critically ill children remain unclear. The objective of this study is to characterize the epidemiology of IVIG use in this population.Methods: We performed a single-center retrospective cohort study of all patients aged between 3 days and 18 years who received at least one IVIG infusion while hospitalized in the pediatric intensive care unit of the Centre hospitalier universitaire (CHU) Sainte-Justine, Montréal Quebec (Canada) between January 1, 2013 and December 31, 2018.Results: One hundred and seventy-two patients received a total of 342 IVIG infusions over the study period. Most common indications for IVIG infusions were staphylococcal or streptococcal toxic shock syndrome (n=53/342, 15.5%), immunoglobulin replacement in chylothorax (n=37/342, 10.9%), prophylaxis following bone marrow transplantation (n=31/342, 9.1%), myocarditis (n=25/342, 7.3%) and post-solid organ transplant complications (n=21/342, 6.1%). The median dose of IVIG per infusion was 0.95 g/kg (IQR 0.5-1.0) and median number of IVIG infusions per patient was one (IQR: 1-2). Seventy-nine percent of IVIG infusions given were administrated for off-label indications with regards to Health Canada recommendations.Conclusion: This study identified the most common indications for IVIG infusion in critically ill children in a tertiary care pediatric intensive care unit. Given the costs, the known adverse events associated with IVIG and the pressure that blood suppliers are facing to meet the demands, clinical trials are needed to evaluate the efficacy and safety of IVIG in conditions where use is significant.

In this issue, Ryan Kirkpatrick and Gordon Boyd speculated on the reasons for the dwindling number of physician scientists in Canada. To help stimulate discussion on this important issue, Clinical and Investigative Medicine invited two distinguished scientists to present their views on this issue.

Purpose: Infliximab (INX) has been approved for treating Crohn disease (CD) for many years, showing promis-ing efficacy in the clinic. However, the efficacy of the drug and the prognosis of CD vary significantly with dif-ferent locations of disease pathology. This study evaluated the efficacy of INX and prognosis in CD in different locations of disease pathology using systematic meta-analysis.

Methods: We used "Infliximab OR Remicade OR Avakine OR Inflectra OR Renflexis OR Remsima OR IgG1k monoclonal antibody" AND "Crohn's disease OR IBD OR inflammatory bowel disease" as search strategies for searching in PubMed, Wanfang and Embase. A systematic meta-analysis for overall proportions was used to analyze the data.

Results: Twelve studies involving 1,978 patients were included. The results confirmed that treatment with INX led to high clinical remission rates (82%, 95% CI: 64%-92%) and low relapse rates (4%, 95% CI: 2%-9%) in patients with CD. Our results also indicated that use of INX in patients with colon only (L2) CD led to lower clinical remission rates, and use of INX in patients with ileum and colon (L3) CD led to higher relapse rates.

Conclusion: Our findings show different remission rates depending on location of the disease and may be useful for clinicians' choice of therapeutics.

Purpose: Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) overexpression has been reported in various types of cancers. The purpose of this study is to clarify the role of NUCKS, underlying the involvement of non-small-cell lung cancer, in the progression of lung cancer.

Methods: The small interfering ribonucleic acid (siRNA) of NUCKS was transfected into a lung cancer cell line (NCI-H460, A549, NCI-H1299 and NCI-H1975). Functional experiments (MTT assay, Annexin V-FITC/PI double staining assay, colony formation assay, wound healing assay and Transwell assay) were performed to measure the effects of NUCKS on lung cancer cell viability, migration, invasion and apoptosis.

Results: NUCKS was found to be up-regulated in lung cancer cells. Knockdown of NUCKS significantly altered lung cancer cell apoptosis, proliferation colony formation, invasion and migration. Moreover, knockdown of NUCKS attenuated the activation of the PI3K/AKT pathway in lung cancer cells.

Conclusion: NUCKS was overexpressed in lung cancer cells and played an important role in lung cancer by increasing cell growth through the PI3K/AKT signalling pathway. This in vitro study suggested NUCKS should be evaluated in a clinical setting as a novel biomarker and potential therapeutic target for lung cancer.

Purpose: Free wall rupture (FWR) is a lethal complication after acute myocardial infarction; however, the un-derlying mechanisms of FWR are unclear. This study analyzes the relationship between neutrophil counts and FWR following ST-elevation myocardial infarction (STEMI).

Methods: The case group was STEMI patients with FWR and the control group was STEMI patients without FWR (case-control ratio was 1:4). The demographic data, clinical manifestation and laboratory test results were retrospectively collected and analyzed.

Results: Of a total of 6,712 consecutive STEMI patients, 78 patients (1.2%) had FWR. Compared with STEMI patients, patients with FWR were older and more likely to be female with an anterior infarct. White blood cell (WBC) counts were significantly higher in the FWR group. Moreover, we found that the elevated neutrophil counts mainly accounted for the elevated WBC counts. There was also a correlation between the age and neu-trophil counts (P=0.0109); as patient age increased, neutrophil counts decreased (P=0.0387). We also found no correlation between neutrophil counts and the time between myocardial infarction attack and FWR; however, when dividing these patients into FWR ≤48 h after admission to hospital for STEMI and FWR >48 h, there was a significant difference in neutrophil counts (P=0.0196). Furthermore, the results of logistic regression analy-sis showed that increased neutrophil was an independent risk factor for FWR (odds ratio: 2.404, confidence interval: 1.055-5.477).

Conclusion: Elevated neutrophil counts were found to be the main cause of differences in WBC counts be-tween FWR and STEMI. Elevated neutrophil was an independent risk factor for FWR. This study provided clues for further research and development of therapeutics for the prevention of FWR.

Purpose: Hematopoietic cell transplantation (HCT) is associated with significant risk prior to hematopoietic engraftment. Endurance exercise can modify the bone marrow microenvironment, alter hematopoiesis and accelerate hematopoietic regeneration in mouse models of transplantation.

Methods: A systematic review was conducted to clarify the impact of exercise on clinically relevant hemato-logical outcomes in patients following HCT.

Results: A systematic search of the literature identified 13 studies (total of 615 participants; 313 in study arms). Studies included exercise regimens that were primarily low-to-moderate intensity. A total of five studies re-ported on engraftment and length of stay, which were largely unchanged with intervention. Rates of graft-ver-sus host disease were reported in six studies whereas red cell and platelet transfusion needs were reported in four studies, neither of which was different with exercise. Survival was reported in four studies and was significantly improved by exercise in one study.

Conclusions: Exercise in patients receiving HCT appears feasible and safe. Heterogeneity in type and intensity of exercise was observed and few studies examined high intensity exercise. Outcome reporting was inconsis-tent regarding transplant-related outcomes. Standardized hematological outcome measures are needed to clarify the impact of higher intensity exercise on HCT.

Purpose: This literature review summarizes the main immunological characteristics of type III interferons (IFN) and highlights the clinically relevant aspects and future therapeutic perspectives for these inflammatory molecules.

Source: Relevant articles in PubMed MEDLINE from the first publication (2003) until 2020. N=101 articles were included in this review.

Principal findings: Type III IFNs represent a relatively newly described inflammatory cytokine family. Although they induce substantially similar signalling to the well-known type I IFNs, significant functional differences make these molecules remarkable. Type III IFNs have extensive biological effects, contributing to the pathogenesis of several diseases and also offering new diagnostic and therapeutic approaches: 1) their potent anti-viral properties make them promising therapeutics against viral hepatitis and even against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is causing the current coronavirus disease 2019 (COVID-19) pandemic; 2) imbalances in the IFN-λs contribute to several forms of chronic inflammation (e.g., systemic and organ-specific autoimmune diseases) and potentially predict disease progression and therapeutic response to biologic therapies; and 3) the antitumor properties of the type III IFNs open up new therapeutic perspectives against malignant diseases.

Conclusion: Over the last 18 years, researchers have gathered extensive information about the presence and role of these versatile inflammatory cytokines in human diseases, but further research is needed to clarify the mechanistic background of those observations. Better understanding of their biological activities will permit us to use type III IFNs more efficiently in new diagnostic approaches and individualized therapies, consequently improving patient care.

Purpose: To estimate the positive predictive value of diagnosis and procedure codes for open and endovascular revascularization for peripheral artery disease (PAD) in Ontario administrative databases.

Methods: We conducted a retrospective validation study using population-based Ontario administrative databases (2005-2019) to identify a random sample of 600 patients who underwent revascularization for PAD at two academic centres, based on ICD-10 diagnosis codes and Canada Classification of Health Intervention procedure codes. Administrative data coding was compared to the gold standard diagnosis (PAD vs. non-PAD) and revascularization approach (open vs. endovascular) extracted through blinded hospital chart re-abstraction. Positive predictive values and 95% confidence intervals were calculated. Combinations of procedure codes with or without supplemental physician claims codes were evaluated to optimize the positive predictive value.

Results: The overall positive predictive value of PAD diagnosis codes was 87.5% (84.6%-90.0%). The overall positive predictive value of revascularization procedure codes was 94.3% (92.2%-96.0%), which improved through supplementation with physician fee claim codes to 98.1% (96.6%-99.0%). Algorithms to identify individuals revascularized for PAD had combined positive predictive values ranging from 82.8% (79.6%-85.8%) to 95.7% (93.5%-97.3%).

Conclusion: Diagnosis and procedure codes with or without physician claims codes allow for accurate identifi-cation of individuals revascularized for PAD in Ontario administrative databases.

Purpose: Post dural puncture headache (PDPH) is a common anesthetic complication caused by expected spinal puncture or accidental dural puncture during intraspinal anesthesia operation. The purpose of this study was to retrospectively analyze the clinical features and outcomes of parturients with accidental dural punctures (ADP).

Methods: (All cesarean sections at the Chongqing Health Center for Women and Children (Chongqing, China) carried out under neuraxial anesthesia from January 1, 2017 to December 31, 2018 were reviewed and data from 20 parturients with ADP were collected and analyzed.

Results: Seventeen individuals received crystal-colloid solution fillers and three did not. The median epidural catheter retaining time was 40 hours; the median frequency of epidural filling was three times, with a median total volume of 60 ml. One patient developed tinnitus and three complained of head swelling during filling. The median bed-stay duration was 73 hours, with total intravenous infusion volume of 7.3 L in the first three postoperative days. Two patients complained of slight dizziness and mitigation, and five felt weak. One individual had intermittent headaches and dizziness till the seventh postoperative day.

Conclusions: Epidural injection of crystal-colloid solution, combined with hydration, maybe a useful preven-tive strategy for ADP-induced headache after cesarean section.